Abstract
Biologic function of the majority of microRNAs (miRNAs) is still unknown. Uncovering the function of miRNAs is hurdled by redundancy among different miRNAs. The deletion of Dgcr8 leads to the deficiency in producing all canonical miRNAs, therefore, overcoming the redundancy issue. Dgcr8 knockout strategy has been instrumental in understanding the function of miRNAs in a variety of cells in vitro and in vivo. In this review, we will first give a brief introduction about miRNAs, miRNA biogenesis pathway and the role of Dgcr8 in miRNA biogenesis. We will then summarize studies performed with Dgcr8 knockout cell models with a focus on embryonic stem cells. After that, we will summarize results from various in vivo Dgcr8 knockout models. Given significant phenotypic differences in various tissues between Dgcr8 and Dicer knockout, we will also briefly review current progresses on understanding miRNA-independent functions of miRNA biogenesis factors. Finally, we will discuss the potential use of a new strategy to stably express miRNAs in Dgcr8 knockout cells. In future, Dgcr8 knockout approaches coupled with innovations in miRNA rescue strategy may provide further insights into miRNA functions in vitro and in vivo.
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Change history
29 April 2019
The section: “miRNA‑independent functions of DICER” was missed between the section “miRNA‑independent functions of DROSHA and DGCR8” and the section “The Dgcr8 knockout strategy to study miRNA functions” in the original publications.
Abbreviations
- APA:
-
Alternative polyadenylation
- AGO:
-
Argonaute
- cKO:
-
Conditional knockout
- cNCCs:
-
Cardiac neural crest cells
- COX-2:
-
Cyclooxygenase 2
- cTECs:
-
Cortical thymic epithelial cells
- DGCR:
-
DiGeorge syndrome chromosomal (or critical) region
- DISME:
-
DGCR8-independent stable miRNA expression strategy
- EMT:
-
Epithelial–mesenchymal transition
- EpiLC:
-
Epiblast-like cells
- EpiSCs:
-
Epiblast stem cells
- ESC:
-
Embryonic stem cell
- ESCC:
-
ESC-specific cell cycle regulating
- GPCs:
-
Glia progenitor cells
- iKO:
-
Inducible knockout
- iPSCs:
-
Induced pluripotent stem cells
- LINE-1:
-
Long interspersed element 1
- lncRNA:
-
Long noncoding RNA
- MC:
-
Microprocessor complex
- miRNA:
-
microRNA
- mTECs:
-
Medullary thymic epithelial cells
- NK:
-
Natural killer
- NSCs:
-
Neural stem cells
- PACT:
-
Protein activator of PKR
- PTA:
-
Persistent truncus arteriosus
- RISC:
-
RNA-induced silencing complex
- RPE:
-
Retinal pigmented epithelium
- rRNA:
-
Ribosomal RNA
- SCs:
-
Schwann cells
- Shh:
-
Sonic hedgehog
- shRNA:
-
Short hairpin RNA
- snoRNA:
-
Small nucleolar RNA
- TDP43:
-
TAR DNA-binding protein 43
- TECs:
-
Thymic epithelial cells
- TRBP:
-
HIV trans-activating response RNA-binding protein
- Th cells:
-
Helper T cells
- tRNA:
-
Transfer RNA
- VSD:
-
Ventricular septal defect
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Acknowledgements
The research in Wang laboratory is supported by the National Key Research and Development Program of China (2016YFA0100701 and 2018YFA0107601) and the National Natural Science Foundation of China (31471222, 31622033, 31821091 and 91640116). WTG is supported by the Fundamental Research Funds for the Central Universities (3332018008). Due to the breadth of this review, we apologize for the unavoidable exclusion of references to research done by many outstanding investigators working in relevant areas.
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Guo, WT., Wang, Y. Dgcr8 knockout approaches to understand microRNA functions in vitro and in vivo. Cell. Mol. Life Sci. 76, 1697–1711 (2019). https://doi.org/10.1007/s00018-019-03020-9
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DOI: https://doi.org/10.1007/s00018-019-03020-9